REMOVAL OF t‐BUTYL AND t‐BUTOXYCARBONYL PROTECTING GROUPS WITH TRIFLUOROACETIC ACID

The trifluoroacetic acid‐mediated removal of t‐butyl groups in protected amino acids leads to the formation of t‐butyl trifluoroacetate. This t‐butyl ester alkylates in trifluoroacetic acid methionine and tryptophan. The t‐butyl trifluoroacetate ester can be destroyed by scavengers commonly employed for t‐butyl cations, and the reaction rates of the scavengers with the ester are used in the evaluation of scavengers. Scavengers of sulphide structure react with t‐butyl trifluoroacetate to form sulphonium compounds, which possess alkylating properties. In the presence of a scavenger during acidolysis, the trifluoroacetic acid and the scavenger will compete in reacting with the t‐butyl cations. Kinetic studies show comparable reaction rates with thiophenol as scavenger. The usefulness of adding scavengers to trifluoroacetic acid in deblocking reactions is due to the removal of t‐butyl trifluoroacetate in addition to the removal of t‐butyl cations. Isobutene reacts with trifluoroacetic acid and yields t‐butyl trifluoroacetate. The reaction reaches an equilibrium displaced in favour of the ester at room temperature. Hence no isobutene can be expected to escape during a deblocking reaction in trifluoroacetic acid.